Mikio Arita

Exercise BP response in subjects with high-normal BP: exaggerated blood pressure response to exercise and risk of future hypertension in subjects with high-normal blood pressure.

OBJECTIVES This study was designed to assess the clinical usefulness of an exaggerated blood pressure (BP) response to exercise (EBPR) in predicting the development of hypertension from a high-normal state. BACKGROUND Exaggerated BP response during both dynamic and isometric exercises are associated with increased risk of future hypertension, while the significance of these responses concerning the identification of individuals with high-normal BP who are prone to develop hypertension is unknown. METHODS The study population comprised a sample of 239 men with high-normal BP (aged 42.3 +/- 5.9 years) who underwent a symptom-limited bicycle ergometer exercise testing at baseline and then were followed for 5.1 years. RESULTS The Kaplan-Meier survival analysis showed that the subjects in the upper quartile of BP response to exercise had a significantly higher cumulative incidence of hypertension on follow-up than those in the middle two and lower quartiles (log-rank test, p < 0.05). Multivariate analysis using the Cox proportional hazards survival model showed that the EBPR was significantly and independently associated with the risk of developing hypertension after adjustment for some traditional risk factors for hypertension (RR = 2.31, 95% confidence interval = 1.45 to 6.25). CONCLUSIONS These findings suggest that an EBPR is an important risk factor for new-onset hypertension from a high-normal state and, thus, exercise testing can provide valid information that may help identify individuals with high-normal BP at a greater risk of future hypertension.

The Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS): Protocol, patient characteristics, and blood pressure during the first 12 months

The benefits of a systolic blood pressure (BP) below 150–160 mmHg are well established; whether a systolic BP of less than 140 mmHg provides additional benefits remains controversial. This study was designed to compare the 2-year effect of a strict treatment to maintain systolic BP below 140 mmHg (group A) and that of a mild treatment to maintain systolic BP at between 140 and below 160 mmHg (group B). The study design followed the Prospective Randomized Open Blinded End-point (PROBE) study. The subjects were elderly patients (65–85 years old) who consistently had a systolic BP of 160 mmHg or higher. The baseline drug was efonidipine hydrochloride (efonidipine), a long-acting dihydropiridine calcium antagonist. The primary endpoints were stroke, cardiac disease, vascular disease, and renal failure. After a run-in period of 2 to 4 weeks, 2,165 patients were assigned to group A and 2,155 patients to group B. There were no significant differences between the groups in sex, age, baseline BP, or other cardiovascular risk factors. The systolic BP was 7.2 mmHg lower (p<0.0001) and the diastolic BP 2.4 mmHg lower (p<0.0001) in group A than in group B after 12 months of treatment. As of this interim analysis, primary endpoints have occurred in 87 patients (stroke in 58 patients, cardiac disease in 27 patients, occlusive arterial disease in 1 patient, and renal failure in 1 patient). Five patients have died of stroke and 2 patients of myocardial infarction. The primary-endpoint-related morbidity rate was 20.9/1,000 patient-years, and the mortality rate was 1.7/1,000 patient-years. Currently available results indicate that this study, one of the largest randomized trials of antihypertensive therapy in elderly patients in Japan, was conducted safely. The final results are expected to provide important and practical information for the management of hypertension in elderly patients.The benefits of a systolic blood pressure (BP) below 150–160 mmHg are well established; whether a systolic BP of less than 140 mmHg provides additional benefits remains controversial. This study was designed to compare the 2-year effect of a strict treatment to maintain systolic BP below 140 mmHg (group A) and that of a mild treatment to maintain systolic BP at between 140 and below 160 mmHg (group B). The study design followed the Prospective Randomized Open Blinded End-point (PROBE) study. The subjects were elderly patients (65–85 years old) who consistently had a systolic BP of 160 mmHg or higher. The baseline drug was efonidipine hydrochloride (efonidipine), a long-acting dihydropiridine calcium antagonist. The primary endpoints were stroke, cardiac disease, vascular disease, and renal failure. After a run-in period of 2 to 4 weeks, 2,165 patients were assigned to group A and 2,155 patients to group B. There were no significant differences between the groups in sex, age, baseline BP, or other cardiovascular risk factors. The systolic BP was 7.2 mmHg lower (p<0.0001) and the diastolic BP 2.4 mmHg lower (p<0.0001) in group A than in group B after 12 months of treatment. As of this interim analysis, primary endpoints have occurred in 87 patients (stroke in 58 patients, cardiac disease in 27 patients, occlusive arterial disease in 1 patient, and renal failure in 1 patient). Five patients have died of stroke and 2 patients of myocardial infarction. The primary-endpoint-related morbidity rate was 20.9/1,000 patient-years, and the mortality rate was 1.7/1,000 patient-years. Currently available results indicate that this study, one of the largest randomized trials of antihypertensive therapy in elderly patients in Japan, was conducted safely. The final results are expected to provide important and practical information for the management of hypertension in elderly patients.

The influence of obesity and metabolic risk variables on brachial-ankle pulse wave velocity in healthy adolescents.

Measurement of brachial-ankle pulse wave velocity (baPWV) is recognized as a simple and practical method for assessing arterial stiffness. We determined whether the baPWV of adolescents is affected by obesity and its associated metabolic risk variables. A cross-sectional sample of 754 apparently healthy adolescents (383 men and 371 women), aged 15–17 years, was recruited for this study. baPWV was measured by a simple automatic oscillometric technique. Adiposity measures, blood pressure, serum lipoproteins, fasting glucose and insulin were evaluated. The baPWV of the adolescents was significantly higher in men than in women and increased with age in both genders. After being statistically adjusted for age and gender, baPWV was significantly correlated with body mass index, percent body fat, waist-to-height ratio, systolic and diastolic blood pressures, mean arterial pressure, triglycerides, high-density lipoprotein cholesterol (HDL-C), atherogenic index, glucose, insulin, and homoeostasis model assessment of insulin resistance (HOMA-IR). In the multivariate regression analysis, mean arterial pressure, atherogenic index, HOMA-IR, systolic blood pressure and age were found to be significant determinants of baPWV (P<0.001). An increasing number of clustered risk variables, including high values (>gender-specific top quartiles) of waist-to-height ratio, mean arterial pressure, atherogenic index and HOMA-IR showed a graded association with baPWV (P<0.001 for trend). These results suggest that obesity and its associated metabolic abnormalities are important factors in the increased baPWV of adolescents and that baPWV may be useful in investigating early arterial wall changes in this population.

A new Ca-antagonist, azelnidipine, reduced blood pressure during exercise without augmentation of sympathetic nervous system in essential hypertension: a randomized, double-blind, placebo-controlled trial.

This study was carried out to evaluate the effect of a new long-acting calcium-channel antagonist, azelnidipine, on hemodynamic and neural responses to exercise. Ten patients (age, 36-69 years) with mild essential hypertension were enrolled in this study. A randomized, double-blind, crossover treatment of azelnidipine at a dose of 8.0 mg once daily for 4 weeks was performed. After a 4-week placebo period, the patients exercised in a submaximal test by using an ergometer with azelnidipine or placebo treatment. The changes caused by exercise in arterial blood pressure (BP), heart rate, cardiac output (CO), and systemic vascular resistance were evaluated. In addition, the plasma norepinephrine (NE), epinephrine (E), plasma renin activity, and plasma aldosterone concentration were determined at rest, at peak exercise, and at the recovery period. Both the SBP and diastolic (D) BP were decreased at rest by azelnidipine treatment (from 158 +/- 10/97 +/- 7 to 145 +/- 14/90 +/- 9 mm Hg). Azelnidipine significantly decreased both SBP and DBP during exercise (SBP, F = 6.09, p < 0.05, Fi = 0.612, NS; DBP, F = 17.78, p < 0.001, Fi = 0.298, NS). No significant changes in the resting heart rate and CO were observed, and the exercise-induced increase of these parameters was also not affected by azelnidipine. Azelnidipine produced no significant change of the resting plasma NE and E levels and an exercise-induced increase of plasma NE. In conclusion, these results indicate that azelnidipine, different from another dihydropyridine-type calcium channel antagonists, does not produce any changes in the hemodynamic and neurohumoral response to exercise, and it may be beneficial for patients with mild essential hypertension.

The angiotensin II receptor blocker telmisartan improves insulin resistance and has beneficial effects in hypertensive patients with type 2 diabetes and poor glycemic control.

The angiotensin II receptor blocker (ARB) telmisartan has a molecular structure that confers it partial agonist properties similar to those of peroxisome proliferators-activated receptor-gamma molecule, which is thought to modulate tissue response to insulin. In order to investigate the effects of telmisartan on insulin sensitivity and glucose metabolism, we enrolled 14 hypertensive patients under treatment with ARB other than telmisartan who had insulin resistance [homeostasis model for insulin resistance (HOMA-IR)>2.0] but no severe glucose tolerance (HbA1c<6.5%), and HOMA-IR was compared before and after the displacement by telmisartan. We also enrolled 27 obese (body mass index>25kg/m(2)) and hypertensive patients with type 2 diabetes under treatment with ARB other than telmisartan, and HbA1c was assessed before and after the displacement by telmisartan. The telmisartan significantly improved HOMA-IR in hypertensive patients and also significantly decreased HbA1c in type 2 diabetic patients especially in the patients with poor glycemic control (HbA1c>==8.0%). These results indicate that telmisartan improves insulin resistance and gives beneficial effects in hypertensive patients with type 2 diabetes and a poor glycemic control.

Increased mean arterial pressure response to dynamic exercise in normotensive subjects with multiple metabolic risk factors.

Metabolic syndrome (MS) may influence vascular reactivity and might cause an excessive increase in blood pressure (BP) during dynamic exercise. We examined this hypothesis in 698 normotensive men (mean age: 43 years) free of cardiovascular disease, diabetes mellitus and renal disease. The response of BP to exercise was assessed by the mean arterial pressure (MAP) during bicycle ergometry. The MAP values were expressed as z-scores normalized to the relative increases in heart rate. High-normal BP, dyslipidemia and hyperglycemia were diagnosed according to the Japan-specific MS criteria. The z-score of MAP was significantly higher in subjects with high-normal BP (+0.57, P<0.001), dyslipidemia (+0.18, P<0.001) and hyperglycemia (+0.24, P<0.001) than in those without MS component (−0.38). In the high-normal BP subjects, the addition of dyslipidemia and/or hyperglycemia was associated with a progressive increase in the z-score of exercise MAP, whereas no such association was observed in the normal-BP subjects (P=0.033, two-way ANOVA). Multivariate regression analysis revealed that a greater number of MS components (β=0.102, P=0.010) was an independent determinant of increased MAP z-score after adjustment for potential confounders, including age (β=0.123, P<0.001), body mass index (β=0.145, P<0.001) and high-normal BP (β=0.410, P<0.001). These results suggest that accumulation of MS components may alter vascular structure and function and lead to the significant elevation of MAP during dynamic exercise even before clinical manifestation of arterial hypertension.

EFFECTS OF LOCALLY ADMINISTERED ARGATROBAN ON RESTENOSIS AFTER BALLOON ANGIOPLASTY: EXPERIMENTAL AND CLINICAL STUDY

1. This study was undertaken to evaluate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin‐induced platelet activation, on restenosis after balloon angioplasty.

Blood pressure and sympathetic activity following responses to aerobic exercise in patients with essential hypertension.

Fourteen untreated patients with essential hypertension (EH) were subjected to mild aerobic exercise with the intensity at 50% of the maximum oxygen uptake (VO2max) twice a week for 12 weeks, as compared with 14 normotensive subjects (NT). Blood pressure and norepinephrine (NE) in plasma, platelet and urine were measured as the indices of sympathetic activity. In EH, a significant fall in both systolic and diastolic blood pressure was observed. In addition, exercise training produced a significant decrease both urinary and platelet NE, but not in plasma NE. Neither significant changes in blood pressure nor NE in plasma, platelet and urine were observed in NT. These results suggest that an inhibition of the sympathetic nervous system might be related to the blood pressure fall in physical exercise training.

Electrocardiographic strain and endomyocardial radial strain in hypertensive patients

BACKGROUND Electrocardiographic strain pattern (ECGS) is a well-recognized marker of the presence and severity of anatomic left ventricular hypertrophy (LVH) and also has been associated with adverse prognosis in hypertensive patients. Left ventricular (LV) endomyocardial radial strain (Endo-RS) is predominant in systolic LV wall thickening compared with epimyocardial radial strain (Epi-RS) in a normal heart. However, it remains unclear whether the ratio of Endo-RS to Epi-RS alters in hypertensive patients, especially in those with ECGS. METHODS Endo-RS and Epi-RS in 9 non-hypertensive subjects (Group A), 26 hypertensive subjects without ECGS (Group B), and 16 hypertensive subjects with ECGS (Group C) were assessed by a tissue tracking system. RESULTS Relative wall thickness, LV mass index, and voltage of SV1+RV5 were significantly greater in Group C than in both Groups A and B. Although no significant difference was seen in Epi-RS among the 3 groups, Endo-RS and the ratio of Endo-RS to Epi-RS (Endo/Epi-RS) in Group C were significantly lower than those in the other two groups. Multiple logistic regression analysis revealed that the only factor which significantly correlated with Endo/Epi-RS in the first tertile (<1.6) was the presence of ECGS (OR=9.28, p=0.01). CONCLUSIONS The appearance of ECGS significantly correlated with not only the development of LV hypertrophy but also with the attenuation of Endo-RS.

Quantitative study on cerebral blood volume determined by a near-infrared spectroscopy during postural change in children

Aim: To investigate changes in cerebral blood volume during standing in healthy children with or without abnormal cardiovascular responses.